Department of Radiation Biology, Radiumhospitalet, Oslo University Hospital, Oslo, Norway.
Department of Radiology, Radiumhospitalet, Oslo University Hospital, Oslo, Norway.
Cancer Res. 2018 Aug 15;78(16):4774-4785. doi: 10.1158/0008-5472.CAN-17-3806. Epub 2018 Jun 26.
The established role of hypoxia-induced signaling in prostate cancer growth, metastasis, and response to treatment suggests that a method to image hypoxia in tumors could aid treatment decisions. Here, we present consumption and supply-based hypoxia (CSH) imaging, an approach that integrates images related to oxygen consumption and supply into a single image. This integration algorithm was developed in patients with prostate cancer receiving hypoxia marker pimonidazole prior to prostatectomy. We exploited the intravoxel incoherent motion (IVIM) signal in diagnostic diffusion-weighted (DW) magnetic resonance (MR) images to generate separate images of the apparent diffusion coefficient (ADC) and fractional blood volume (fBV). ADC and fBV correlated with cell density (CD) and blood vessel density (BVD) in histology and whole-mount sections from 35 patients, thus linking ADC to oxygen consumption and fBV to oxygen supply. Pixel-wise plots of ADC versus fBV were utilized to predict the hypoxia status of each pixel in a tumor and to visualize the predicted value in a single image. The hypoxic fraction (HF) of CSH images correlated strongly ( = 0.66; = 41) with pimonidazole immunoscore (HS); this relationship was validated in a second pimonidazole cohort ( = 0.54; = 54). We observed good agreement between CSH images and pimonidazole staining in whole-mount sections. HF correlated with tumor stage and lymph node status, consistent with findings for HS Moreover, CSH imaging could be applied on histologic CD and BVD images, demonstrating transferability to a histopathology assay. Thus, CSH represents a robust approach for hypoxia imaging in prostate cancer that could easily be translated into clinical practice. These findings present a novel imaging strategy that indirectly measures tumor hypoxia and has potential application in a wide variety of solid tumors and other imaging modalities. http://cancerres.aacrjournals.org/content/canres/78/16/4774/F1.large.jpg .
缺氧诱导信号在前列腺癌生长、转移和治疗反应中的既定作用表明，一种能够在肿瘤中成像缺氧的方法可以辅助治疗决策。在这里，我们提出了基于耗氧和供氧的缺氧（CSH）成像，这是一种将与氧消耗和供氧相关的图像整合到单个图像中的方法。这种整合算法是在接受前列腺癌切除术的患者中使用缺氧标志物 pimonidazole 之前开发的。我们利用诊断性弥散加权（DW）磁共振（MR）图像中的体素内不相干运动（IVIM）信号，生成表观弥散系数（ADC）和部分血容量（fBV）的单独图像。ADC 和 fBV 与组织学和 35 例患者的全器官切片中的细胞密度（CD）和血管密度（BVD）相关，因此将 ADC 与氧消耗相关联，fBV 与氧供应相关联。ADC 与 fBV 的像素比图用于预测肿瘤中每个像素的缺氧状态，并在单个图像中可视化预测值。CSH 图像的低氧分数（HF）与 pimonidazole 免疫评分（HS）强烈相关（=0.66；n=41）；这一关系在第二个 pimonidazole 队列中得到了验证（=0.54；n=54）。我们在全器官切片中观察到 CSH 图像与 pimonidazole 染色之间的良好一致性。HF 与肿瘤分期和淋巴结状态相关，与 HS 的发现一致。此外，CSH 成像可应用于组织学 CD 和 BVD 图像，证明了其在组织病理学检测中的可转移性。因此，CSH 代表了一种用于前列腺癌缺氧成像的强大方法，很容易转化为临床实践。这些发现提出了一种新的间接测量肿瘤缺氧的成像策略，在各种实体瘤和其他成像方式中具有潜在的应用。http://cancerres.aacrjournals.org/content/canres/78/16/4774/F1.large.jpg。
